EMT Subtype Influences Epithelial Plasticity and Mode of Cell Migration.
EMT Subtype Influences Epithelial Plasticity and Mode of Cell Migration.
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EMT亚型影响上皮可塑性和细胞迁移模式。
DOI：
10.1016/j.devcel.2018.05.027
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发表时间：
2018-06-18
影响因子：
11.8
通讯作者：
Stanger BZ
中科院分区：
文献类型：
--
作者：
Aiello NM;Maddipati R;Norgard RJ;Balli D;Li J;Yuan S;Yamazoe T;Black T;Sahmoud A;Furth EE;Bar-Sagi D;Stanger BZ
上皮间质转化（EMT）与肿瘤细胞的侵袭和转移密切相关。认为EMT主要通过EMT转录因子的抑制活性在转录水平上调节。然而，这些经典的机制已经解析出几乎完全在体外，留下的问题的程序驱动EMT在生理环境中。在这里，使用谱系标记的胰腺导管腺癌的小鼠模型来研究体内EMT，我们发现大多数肿瘤通过涉及蛋白质内化而不是转录抑制的替代程序失去其上皮表型，导致“部分EMT”表型。利用该程序的癌细胞作为簇迁移，与传统定义的EMT机制相关的单细胞迁移模式形成对比。此外，许多乳腺癌和结直肠癌细胞系利用这种替代方案进行EMT。总的来说，这些结果表明，癌细胞有不同的方式失去他们的上皮程序，导致不同的模式的入侵和传播。Aiello等人使用谱系追踪的肿瘤模型描述了上皮-间充质转化（EMT）的程序，其在几种癌中是保守的，涉及上皮蛋白的重新定位而不是转录抑制。这种替代方案导致“部分EMT”表型，其促进集体肿瘤细胞迁移和循环肿瘤细胞簇的形成。
Epithelial-mesenchymal-transition (EMT) is strongly implicated in tumor cell invasion and metastasis. EMT is thought to be regulated primarily at the transcriptional level through the repressive activity of EMT transcription factors. However, these classical mechanisms have been parsed out almost exclusively in vitro, leaving questions about the programs driving EMT in physiological contexts. Here, using a lineage-labeled mouse model of pancreatic ductal adenocarcinoma to study EMT in vivo, we found that most tumors lose their epithelial phenotype through an alternative program involving protein internalization rather than transcriptional repression, resulting in a “partial EMT” phenotype. Carcinoma cells utilizing this program migrate as clusters, contrasting with the single-cell migration pattern associated with traditionally-defined EMT mechanisms. Moreover, many breast and colorectal cancer cell lines utilize this alternative program to undergo EMT. Collectively, these results suggest that carcinoma cells have different ways of losing their epithelial program, resulting in distinct modes of invasion and dissemination. Using a lineage-traced tumor model, Aiello et al. describe a program of epithelial-to-mesenchymal transition (EMT), conserved across several carcinomas, involving re-localization of epithelial proteins rather than transcriptional repression. This alternative program leads to a “partial EMT” phenotype that promotes collective tumor cell migration and formation of circulating tumor cell clusters.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.5
作者：
Cheung KJ;Gabrielson E;Werb Z;Ewald AJ
通讯作者：
Ewald AJ
DOI：
10.1073/pnas.0810111105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Jean-Paul, De La O.;Emerson, Lyska L.;Murtaugh, L. Charles
通讯作者：
Murtaugh, L. Charles
DOI：
10.1073/pnas.0810097105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Habbe, Nils;Shi, Guanglu;Maitra, Anirban
通讯作者：
Maitra, Anirban
影响因子：
3.8
作者：
Anastassiou D;Rumjantseva V;Cheng W;Huang J;Canoll PD;Yamashiro DJ;Kandel JJ
通讯作者：
Kandel JJ